Process of producing nicotinic acid



Patented Feb. 12, 1946 PROCESS OF PRODUCINGNICOTINIO ACID Adolph Zimmerli, Highland Park. N. J.

Drawing. Application March 1942,

Serial No. 433.325 r 7 Claims. (Cl. 260-2955) I The present invention relates to a process for producing nicotinic acid as the end product, but contemplates the formation of an intermediate product as the first phase of the treatment, which intermediate product constitutes the base material from which the end product isultimately derived.

More particularly my invention relates to a process for producing nicotinic acid by the treat-' ment of 5,7-dinitro-8-quinolinol, with nitric acid. The first phase of the treatment results in the production of quinolinic acid nitrate as an intermediate product, from which quinolinic acid may or may not be isolated, but which in either case serves as the base material for the production of nicotinic acid therefrom. From a chemical standpoint, it is immaterial whether the main process is carried out to its completion as a continuous process without interruption; or interrupted and subsequently continued by using the intermediate product as a base for the direct production of nicotinic acid, by merely utilizing a latter phase of the complete process as a separate process. In other words my completeprocess comprises several phases which has as the initial phase the production of quinolinic acid nitrate, by the actionof nitric acid on Fill-dinitro-B-quinolinol, as an intermediate product which latter may or may not be treated to isolate quinolinic acid therefrom. From this intermediate product nicotinic acid is produced as a con tinuous or separate phase of the entire process.

An object of the invention is the preparation of nicotinic acid cheaply, safely and in large quantities. A special object is toprovide a process for producing nicotinic acid from a starting ess without interruption or in its separate phases.

Other objects of the invention will become mrznifest from the examples followinghereina er.

Nicotinic acid has been preparedaccording to the prior art from pyridines, substituted in the 3 position, by substitution or oxidation, or from quinolinic acid by the splitting of! of CO: by heat or acids.

quinolinic acid in been produced from numerous compounds of the quinoline series.

The oxidation of unsubstituted quinoline gives very poor yields because the pyridine ring is as easily destroyed as the benzenering.

5 Derivatives of quinoline, substituted inthe benzene ring are attacked by acidic oxidizing agents more easily, leading to the destruction of the benzene ring while the pyridine ring remains intact. The oxidation of 8-quinoline-sulfonic acid, 8,-quinolinol, and alizarineindigoblue has been described in the literature.

All of these methods are either using very expensive materials or materials available only in limited amounts, give low yields or proceed with extreme violence. For example, explosions have occurred when quinolinol was oxidized with nitric acid, thereactiori being so strongly exothermic that it was impossible to keep the temperature within bounds, especially when working with batches of commercial size. I

For successful operation on alarge scale it was necessary to find a compound that could be oxidized safely, cheaply and give a good yield of nicotinic acid. My search for a quinoline derivative answering these specifications finally led me to the use of 5,7-dinitro-8-quinolinol as'the start-' ing material.

5,7-dinitro-8-quinolinol may be prepared in very good yield by the methods generally used for 30 the nitration of phenols and naphthols. However, 'as prepared heretoiore by workers of the prior art; there,ia no unanimity as to its properties. I have found that this could largely be corrected by a method of purification which con-- 'sists in the recrystallization of the crude product as obtained by nitration of 8-quino1inol, from'denaturing grade pyridine in which itis soluble at the boiling point to the extent oi! 13 parts in -100 parts of solvent. On cooling it crystallizes in thin elongated yellow leaflets, containing solvent of crystallization which evaporates on dryin leaving 5,7-dinitro 8-quinolinol as a yellow powder which decomposes suddenly without melting when heated to 320 C. r 45 I have discovered that 5,7-dinitro-8-quinolinol offers enough resistance to oxidation so that it is attacked comparatively slowly by nitric acid of proper concentration. The reaction takes place stepwise and may be easily controlled by regulation of the concentrationand temperature. It can be stopped, for example, when most of it has been converted into quinolinic acid nitrate, or it can be carried through to nicotinic acid without the isolation of an'intermediate compound. such as quinolinic acid.

From 2 to 4 parts of 100% nitric acid or a. corresponding amount of weaker acid are needed to complete the reaction. It proceeds slowly with very dilute acid, reaches a convenient speed with an acid of from 40% to 70% strength and has to be watched carefully if stronger acid is used.

The nitrous oxides formed bythe reduction of .the nitric acid may be reoxidized, absorbed and concentrated in known manner and used over and over so that only the comparatively small unavoidable loss through incomplete absorption has to be compensated by fresh nitric acid,thereby reducing the cost of the oxidizing agent to a small item. I

; .My complete process in its major phases may be represented by the structure In practicing my invention I may suspend crystals of 5,7-dinltro-8-quinolinol in dilute nitric acid. By proper control of] acid concentration and temperature, hereinafter more fully illustrated by specific, examples, I first pro'duce'quinolinic' acid nitrate as an intermediate product, from which duinolinic acid may be isolated by the addition of water, but preferably is not isolated so as to allow the uninterrupted carrying out of the complete process'to the end product.

In this latter phase I heat the quinolinic acid nitrate either alone or with more nitric acid to higher temperatures. V The invention, although not limited thereto,

. will be 'further illustrated by the following specific examplesthe parts being by weight:

Example 1.-Nicotim'c acid prepared directly,

i. e., withoutisolatiori step Example 2.-Nicotinic acid prepareddirectly, i. e.,

a without isolation step ;'The crude nitration product from quinolinol,

consisting of a suspension of 5,7-dinitro-8-quinolinol in dilute nitric acid, is heated to boiling.

The distilling water is replaced by nitric acid of 68% strength until all the 5,7-dinitro-8-quinolin'ol has disappeared. keeping the volume constant to this point. The heating and concentration is then continued as described in Example 1. The crude nicotinic acid, having a purity of 85-95% is then purified by sublimation or crystallization or a combination of both.

Example 3Q-Quinolinic acid nitrate isolated A suspension of 500 parts 5,7-dinitro-8 quinolinol in 500 parts nitric acid of 40% strength is heated to boiling. While refluxing, 900 parts 98% 1 nitric acid are added graduallyat such a speed that there .is continuous evolution of nitrous fumes without ever allowing the reaction to become violent. After all the acid has been added the refluxing iscontinued until the evolution of nitrous fumes practically ceases. The solution is then emptied into a shallow steam heated kettle f and the heating continued until the liquid solidifies into a cake of quinolinic acid nitrate. After cooling 1000 parts water are added and the sus- I pension of quinolinic acid filtered oil.

1 Exam le 4.Nicotinic acid, as and product, in-

eluding isolation step 500 parts5,7-dInitro-8-quinolinol are added to 4500 parts nitric acid of 30%- strength. Water and nitrous oxides are distilled until a clear solution of quinolinic acid nitrate is formed. This solution is thenpoured slowly intoa vessel being any known manner.

kept at 200 C. to 240". C. After all has been added, the heating is continued until gassing ceases. After cooling, the nicotinic acid, weigh ing about 220 parts, is broken up and purifiedin It will be understood that the various examples herein set forth are given as merely illustrative of the various phases in which my invention may i be practicedwithout departing from the spirit thereof. The invention in its broadest aspects comprises several phases or serlesof steps, the first phase resulting in the production of asubstance which may be regarded-as an intermediate I product.

Although my process permits of the 1 isolation of suchintermediate product, it is conce'rned primarily as affording a continuous process for producing the desired end product, and

I wish protection of the process, practiced with or without interruption,-as defined by the appended claims.v

What is claimed is: 1. The process of producing quinolinic acid hi i trate comprising adding in the absence of hydrochloric acid approximately 500 parts 5, '7, di-

1 nitro-8-quinolinol over a period of from 6 to 8 hours to about 1800 parts nitric acid of percent, strength at 100 degrees centigrade and j evaporating to dryness. v

2. The process of producing nicotinic acid,

comprising adding in the absence-o hydrochloric 1800 parts nitric acid of 60 percent strength at acid approximately 500 parts 5, 7, dinitro-8- quinolinol over a period of about 6 hours to about I 100 degrees centigrades,- then gradually heating the mixture in the-absence of hydrochloric acid tigrade until the evolution of nitrous fumes and over'a period of about 8 hours to 240 degrees cencarbon dioxide ceases.

3. The process of producing nicotinic acid,

comprising heating 5,7-dinitro-8-qulnolinol with nitric acid only of from 30 to 100 per cent strength I until substantial quantities of nitrous oxide fumes are given off, this first phase of the treatment resulting in theproduction of quinolinic acid nitrate as an intermediate product, and continuing the treatment without isolating quinolinic acid by.

heating the quinolinic' acid nitrate to 200-240 degrees centigrade until 'decarboxylation and de- 1 nitration occurs with the evolution of carbon dioxide and nitrous oxide fumes, and recovering the nicotinic acid.

4. The process of producing nicotinic acid comprising treating 5,7-dinitro-8-quino1inol in the absence of hydrochloric acid with from 3 to 6 parts nitric acid of about 65 per cent strength, heating to boiling, adding concentrated nitric acid, evaporating to dryness, and heating to 200 to 240 degrees centigrade until the solid remelts.

5. The process of forming quinolinic acid nitrate as an intermediate product in the production of nicotinic acid comprising treating 5,7 dinltro-B-quinolinol in the presence of nitric acid of from 30 to 100 per cent strength and in the absence of hydrochloric acid by heating to temperatures of from 100 to 120 degrees centigrade until substantial quantities of nitric oxide fumes ane given on.

6. The process of producing nicotinic acid comprising boiling 5,7-dinitro-8-quinolinol-only with nitric acid of from 30 to 100 per cent strength to form quinolinic acid nitrate and continuing the treatment by heating to 200 to'240 degrees centigrade to convert the quinolinic acid nitrate into nicotinic acid.

'7. The process of producing nicotinic acid comprising treating 5,7-dinitro-8-quinolinol in the absence of/hydrochloric acid with nitric acid of from 30 to 100 per cent strength, heating to a temperature of about 100 degrees centigrade u'ntil substantial quantitiesof nitrous oxide Iumesaregiven on, thereafter raising the temperature to from 200 to- 240 degrees centigrade until decarboxylation and denitration occurs with theevolution of carbon dioxide-and nitrous oxide iumes, and recovering the nicotinic acid.

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